Abstract
Colorectal cancer (CRC) is one of the most common cancers in the world. Despite improvements in screening for early diagnosis, CRC is one of the leading causes of cancer deaths. The aim of the study was to determine a potential association between the frequency of GSTM1 and GSTT1 null genotypes and the risk of CRC in the Polish population. Moreover, we analyzed the clinical parameters with the glutathione S-transferase (GST) gene polymorphisms in patients with CRC. The study was conducted on 512 Caucasians, including 279 patients (105 women and 174 men) with CRC. DNA from peripheral blood was extracted and the multiplex polymerase chain reaction (PCR) technique was used for glutathione S-transferase theta (GSTT1) and mu (GSTM1) gene deletion genotyping. We found no statistically significant differences in the frequency of the GST gene polymorphisms in patients with CRC and controls. The prevalence of the GSTM1*0 variant in the test subjects was higher than in controls (45.9% vs 42.9%; p > 0.05). The frequency of the GSTT1*0 variant was also higher in patients with CRC compared to the control population (21.1% vs 18.9%; p > 0.05). In addition, the effect of the GSTM1 and GSTT1 polymorphisms on the incidence of CRC was also analyzed. There was a slight, but not statistically significant, increase of the risk of colon cancer for the GSTM1*0 and GSTT1*0 variants. Moreover, we examined the GST genotype due to the cancer TNM classification and the location of the primary tumor. Statistically significant differences in the distribution of the GSTT1*0 and GSTT1*1 genotypes in both the stage and the location of the primary tumor were observed. It is suggested that the GSTT1 polymorphism may have an impact on the severity of the tumor and its location.
Highlights
Colorectal cancer (CRC) occurs most commonly in developed countries and it is the second most frequent tumor in Poland
We found no statistically significant differences in the frequency of the glutathione S-transferase (GST) gene polymorphisms in patients with CRC and controls
According to the pathological TNM classification, we identified preinvasive carcinoma (Tis) in 7 cases (2.5%), the tumor invading the muscularis propria (T2) in 40 patients (14.3%), while in 153 cases (54.8%), we found the features of T3, with the tumor invading through the muscularis propria into pericolorectal tissues
Summary
Colorectal cancer (CRC) occurs most commonly in developed countries and it is the second most frequent tumor in Poland. The dynamic increase in the number of CRC cases makes Poland a leader among EU countries in the incidence of this disease entity. Several studies present the attempt to use the genotypes of phase II detoxification enzymes – glutathione S-transferase (GST), UDPglucuronosyltransferase (UGT), sulfotransferase (SULT), and N-acetyltransferase (NAT) – as molecular markers of cancer risk. GST was the subject of a number of studies as a potential susceptibility gene for colon cancer.[2,3] Glutathione S-transferases (GSTs) are a superfamily of multifunctional proteins that play an important role in cellular detoxification. It has been shown that the activity of GST in tumor cells may be associated with their resistance to chemotherapeutic drugs, because the level of the GST activity in cancer cells is probably significantly increased and may influence the outcome of the treated patients. Despite improvements in screening for early diagnosis, CRC is one of the leading causes of cancer deaths
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